Recent evidence suggests the existence of fundamental relationships between B-cell dependent humoral immunity and T cell-dependent cell- mediated immunity (CMI). Examples of reciprocal B-cell - T-cell augmenting and suppressing regulatory processes have been described. The proposed research has as its objective the definition of the role of specific humoral antibodies in the development and expression of cell- mediated immunity. One approach will be to isolate the individual classes of specific antibodies from immune sera and to examine their effects on various parameters of cell mediated immunity in vivo and in vitro. In the proposed studies we will be specifically looking for evidence that antibody molecules of certain classes can exert physiological regulatory influences on cell-mediated immune reactions and to what extent other classes of antibodies present in the same serum can interfere with these regulatory effects. A second method to assess the regulatory role of specific antibodies on T-cell dependent immunological reactions will be to study CMI in animals with specific immunoglobulin deficiencies created by the administration of anti-heavy chain antisera. CMI reaction will be examined in animals treated with immunosuppressive doses of heterologous anti rM, rG and rA globulins to determine the effect of selective removal of antibodies on the development of CMI. The definition of specific regulatory elements in the complex milieu of serum immunoglobulins would have important implications in relation to predictably modifying the immune responses in prophylaxis and in handling of such clinical problems as allergic disorders, autoimmune diseases, tissue allografting and tumor therapy.